Major and minor metabolites of cocaine in human plasma following controlled subcutaneous cocaine administration

Erin A. Kolbrich, Allan J. Barnes, David A. Gorelick, Susan J. Boyd, Edward J. Cone, Marilyn A. Huestis

Research output: Contribution to journalArticle

Abstract

Cocaine is rapidly metabolized to major metabolites, benzoylecgonine (BE) and ecgonine methyl ester (EME), and minor metabolites, norcocaine, p-hydroxycocaine, m-hydroxycocaine, p-hydroxybenzoylecgonine (pOHBE), and m-hydroxybenzoylecgonine. This IRB-approved study examined cocaine and metabolite plasma concentrations in 18 healthy humans who provided written informed consent to receive low (75 mg/70 kg) and high (150 mg/70 kg) subcutaneous cocaine hydrochloride doses. Plasma specimens, collected prior to and up to 48 h after dosing, were analyzed by gas chromatography-mass spectrometry (2.5 ng/mL limits of quantification). Cocaine was detected within 5 min, with mean ± SE peak concentrations of 300.4 ± 24.6 ng/mL (low) and 639.1 ± 56.8 ng/mL (high) 30-40 min after dosing. BE and EME generally were first detected in plasma 5-15 min post-dose; 2-4 h after dosing, BE and EME reached mean maximum concentrations of 321.3 ± 18.4 (low) and 614.7 ± 46.0 ng/mL (high) and 47.4 ± 3.0 (low) and 124.4 ± 18.2 ng/mL (high), respectively. Times of last detection were BE > EME > cocaine. Minor metabolites were detected much less frequently for up to 32 h, with peak concentrations ≤ 18 ng/mL for all analytes except pOHBE (up to 57.7 ng/mL). These data improve our knowledge of the pharmacokinetics of cocaine and its major and minor metabolites in plasma following controlled subcutaneous cocaine administration.

Original languageEnglish (US)
Pages (from-to)501-510
Number of pages10
JournalJournal of Analytical Toxicology
Volume30
Issue number8
StatePublished - 2006

Fingerprint

Plasma (human)
Metabolites
Cocaine
metabolite
ester
Esters
plasma
Plasmas
Pharmacokinetics
Gas chromatography
Mass spectrometry
gas chromatography
Research Ethics Committees
mass spectrometry
Informed Consent
Gas Chromatography-Mass Spectrometry
benzoylecgonine
ecgonine methyl ester

ASJC Scopus subject areas

  • Analytical Chemistry
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Kolbrich, E. A., Barnes, A. J., Gorelick, D. A., Boyd, S. J., Cone, E. J., & Huestis, M. A. (2006). Major and minor metabolites of cocaine in human plasma following controlled subcutaneous cocaine administration. Journal of Analytical Toxicology, 30(8), 501-510.

Major and minor metabolites of cocaine in human plasma following controlled subcutaneous cocaine administration. / Kolbrich, Erin A.; Barnes, Allan J.; Gorelick, David A.; Boyd, Susan J.; Cone, Edward J.; Huestis, Marilyn A.

In: Journal of Analytical Toxicology, Vol. 30, No. 8, 2006, p. 501-510.

Research output: Contribution to journalArticle

Kolbrich, EA, Barnes, AJ, Gorelick, DA, Boyd, SJ, Cone, EJ & Huestis, MA 2006, 'Major and minor metabolites of cocaine in human plasma following controlled subcutaneous cocaine administration', Journal of Analytical Toxicology, vol. 30, no. 8, pp. 501-510.
Kolbrich, Erin A. ; Barnes, Allan J. ; Gorelick, David A. ; Boyd, Susan J. ; Cone, Edward J. ; Huestis, Marilyn A. / Major and minor metabolites of cocaine in human plasma following controlled subcutaneous cocaine administration. In: Journal of Analytical Toxicology. 2006 ; Vol. 30, No. 8. pp. 501-510.
@article{3abe4f76aba74f50915038613925e1ff,
title = "Major and minor metabolites of cocaine in human plasma following controlled subcutaneous cocaine administration",
abstract = "Cocaine is rapidly metabolized to major metabolites, benzoylecgonine (BE) and ecgonine methyl ester (EME), and minor metabolites, norcocaine, p-hydroxycocaine, m-hydroxycocaine, p-hydroxybenzoylecgonine (pOHBE), and m-hydroxybenzoylecgonine. This IRB-approved study examined cocaine and metabolite plasma concentrations in 18 healthy humans who provided written informed consent to receive low (75 mg/70 kg) and high (150 mg/70 kg) subcutaneous cocaine hydrochloride doses. Plasma specimens, collected prior to and up to 48 h after dosing, were analyzed by gas chromatography-mass spectrometry (2.5 ng/mL limits of quantification). Cocaine was detected within 5 min, with mean ± SE peak concentrations of 300.4 ± 24.6 ng/mL (low) and 639.1 ± 56.8 ng/mL (high) 30-40 min after dosing. BE and EME generally were first detected in plasma 5-15 min post-dose; 2-4 h after dosing, BE and EME reached mean maximum concentrations of 321.3 ± 18.4 (low) and 614.7 ± 46.0 ng/mL (high) and 47.4 ± 3.0 (low) and 124.4 ± 18.2 ng/mL (high), respectively. Times of last detection were BE > EME > cocaine. Minor metabolites were detected much less frequently for up to 32 h, with peak concentrations ≤ 18 ng/mL for all analytes except pOHBE (up to 57.7 ng/mL). These data improve our knowledge of the pharmacokinetics of cocaine and its major and minor metabolites in plasma following controlled subcutaneous cocaine administration.",
author = "Kolbrich, {Erin A.} and Barnes, {Allan J.} and Gorelick, {David A.} and Boyd, {Susan J.} and Cone, {Edward J.} and Huestis, {Marilyn A.}",
year = "2006",
language = "English (US)",
volume = "30",
pages = "501--510",
journal = "Journal of Analytical Toxicology",
issn = "0146-4760",
publisher = "Preston Publications",
number = "8",

}

TY - JOUR

T1 - Major and minor metabolites of cocaine in human plasma following controlled subcutaneous cocaine administration

AU - Kolbrich, Erin A.

AU - Barnes, Allan J.

AU - Gorelick, David A.

AU - Boyd, Susan J.

AU - Cone, Edward J.

AU - Huestis, Marilyn A.

PY - 2006

Y1 - 2006

N2 - Cocaine is rapidly metabolized to major metabolites, benzoylecgonine (BE) and ecgonine methyl ester (EME), and minor metabolites, norcocaine, p-hydroxycocaine, m-hydroxycocaine, p-hydroxybenzoylecgonine (pOHBE), and m-hydroxybenzoylecgonine. This IRB-approved study examined cocaine and metabolite plasma concentrations in 18 healthy humans who provided written informed consent to receive low (75 mg/70 kg) and high (150 mg/70 kg) subcutaneous cocaine hydrochloride doses. Plasma specimens, collected prior to and up to 48 h after dosing, were analyzed by gas chromatography-mass spectrometry (2.5 ng/mL limits of quantification). Cocaine was detected within 5 min, with mean ± SE peak concentrations of 300.4 ± 24.6 ng/mL (low) and 639.1 ± 56.8 ng/mL (high) 30-40 min after dosing. BE and EME generally were first detected in plasma 5-15 min post-dose; 2-4 h after dosing, BE and EME reached mean maximum concentrations of 321.3 ± 18.4 (low) and 614.7 ± 46.0 ng/mL (high) and 47.4 ± 3.0 (low) and 124.4 ± 18.2 ng/mL (high), respectively. Times of last detection were BE > EME > cocaine. Minor metabolites were detected much less frequently for up to 32 h, with peak concentrations ≤ 18 ng/mL for all analytes except pOHBE (up to 57.7 ng/mL). These data improve our knowledge of the pharmacokinetics of cocaine and its major and minor metabolites in plasma following controlled subcutaneous cocaine administration.

AB - Cocaine is rapidly metabolized to major metabolites, benzoylecgonine (BE) and ecgonine methyl ester (EME), and minor metabolites, norcocaine, p-hydroxycocaine, m-hydroxycocaine, p-hydroxybenzoylecgonine (pOHBE), and m-hydroxybenzoylecgonine. This IRB-approved study examined cocaine and metabolite plasma concentrations in 18 healthy humans who provided written informed consent to receive low (75 mg/70 kg) and high (150 mg/70 kg) subcutaneous cocaine hydrochloride doses. Plasma specimens, collected prior to and up to 48 h after dosing, were analyzed by gas chromatography-mass spectrometry (2.5 ng/mL limits of quantification). Cocaine was detected within 5 min, with mean ± SE peak concentrations of 300.4 ± 24.6 ng/mL (low) and 639.1 ± 56.8 ng/mL (high) 30-40 min after dosing. BE and EME generally were first detected in plasma 5-15 min post-dose; 2-4 h after dosing, BE and EME reached mean maximum concentrations of 321.3 ± 18.4 (low) and 614.7 ± 46.0 ng/mL (high) and 47.4 ± 3.0 (low) and 124.4 ± 18.2 ng/mL (high), respectively. Times of last detection were BE > EME > cocaine. Minor metabolites were detected much less frequently for up to 32 h, with peak concentrations ≤ 18 ng/mL for all analytes except pOHBE (up to 57.7 ng/mL). These data improve our knowledge of the pharmacokinetics of cocaine and its major and minor metabolites in plasma following controlled subcutaneous cocaine administration.

UR - http://www.scopus.com/inward/record.url?scp=33750183625&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750183625&partnerID=8YFLogxK

M3 - Article

C2 - 17132243

AN - SCOPUS:33750183625

VL - 30

SP - 501

EP - 510

JO - Journal of Analytical Toxicology

JF - Journal of Analytical Toxicology

SN - 0146-4760

IS - 8

ER -